Project Summary/Abstract In-vivo neuronal intracellular recordings contain rich, functional information at unparalleled spatial and temporal resolution and are generally considered fundamental to testing hypotheses about brain function and dysfunction. However, they are extremely difficult to obtain in vertebrate animals with current technology. Consequently, even highly skilled Neurophysiologists are able to record intra-cellular activity for only 45 min to a maximum of few hours in anesthetized vertebrate animals with rare instances of successful recordings from awake, behaving animals for very short durations. The overall goal of the current proposal is to develop a head-mounted system for recording intra-cellular membrane potentials in vivo from ensembles of neurons in anesthetized animals initially and subsequently in awake, behaving animals. We propose to use Micro-electromechanical systems (MEMS) based technologies to dramatically reduce the form factor and develop a head-mounted, autonomous nanoelectrode system that will (a) automate and minimize the art in intracellular recording experiments and (b) enable intra-cellular recordings from single neurons in anesthetized animals. We will build on our past success in developing MEMS movable microelectrode systems for chronic recording of single and multi-unit activity from the brain in vivo. The specific aims of the proposal are to (a) design, develop and test a nanoelectrode system that will autonomously position the nanoelectrode inside a xenopus oocyte cell and record membrane potentials and (b) test the autonomous nanoelectrode system for its ability to record stable intracellular potentials in isolated abdominal ganglia from Aplysia, rat hippocampal brain slices and finally in anesthetized adult rat models. Successful completion of the project goals will make intracellular recording technology more readily available for rodent experiments and will therefore impact a wide range of neurophysiological studies. The nanoelectrode approach proposed here is also readily scalable to realize higher channel counts to record intracellular activity from ensembles of neurons to capture emergent functional correlates to behavior.